Adding the FcRn antagonist efgartigimod for the prevention of IgG-mediated complications in the peri-transplant period.

BACKGROUND

The management of IgG-mediated diseases in the peri-allogeneic transplant period remains challenging. Specifically, the presence of donor-specific antibodies (DSA) is a major cause of graft failure and poor graft function; despite improvements in desensitization, it remains an unmet need. Similarly, there is no standard approach for the prevention of delayed RBC transfusion independence and pure red blood cell aplasia caused by IgG isoagglutinins after major ABO-mismatched transplant. We describe the first use of the FcRn antagonist efgartigimod to assist in preventing both issues in a patient with high DSA undergoing major ABO-mismatched transplant.

CASE REPORT: A woman with molecular relapse of FLT3-ITD+ AML with no available haploidentical donors and a poor donor search underwent a myeloablative stem cell transplant from a major ABO-mismatched (A donor into O recipient), 6/8 HLA-matched unrelated donor. Prior to conditioning chemotherapy, DSA remained above a median fluorescent intensity (MFI) of 8000 despite rituximab, daratumumab, IVIG, and plasma exchange. Efgartigimod was given on days -3, +4, and +11 of transplant, resulting in a prompt decrease of DSA and anti-A isohemagglutinins and successful engraftment, including rapid RBC transfusion independence.

DISCUSSION: Desensitization strategies for patients with high DSA or high isohemagglutinins remain imperfect and time consuming. The use of FcRn antagonists such as efgartigimod, which reduce recycling of IgG, including pathogenic IgG antibodies, complements the plasma and lymphocyte depleting activity of conditioning therapy and posttransplant cyclophosphamide and may be an effective adjunct in the management of IgG-mediated processes in the posttransplant period.